Abiraterone Acetate in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer. (ABIDO)

Abiraterone Acetate Maintenance in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer. Randomized Phase II Study.

Prostate cancer is the most frequently diagnosed non-skin cancer, and the second leading cause of men cancer death in the United States. Hormonal therapy remains a first-line treatment for metastatic prostate cancer. Initial responses to hormonal therapy with chemical or surgical castration are quite favorable, however, most patients will progress to a castration-resistant phase of the disease. Docetaxel is the primary chemotherapeutic option for patients with mCRPC.

Abiraterone is a novel, selective, irreversible, and potent inhibitor of 17-[alpha]-hydroxylase/17,20-lyase (CYP17) enzymatic activity that has recently been demonstrated to further reduce testosterone levels in the blood to undetectable range (< 1 ng/dL) and is suggested to reduce de novo intratumor androgen synthesis. Abiraterone demonstrated activity in castration resistant prostate cancer patients previously treated with docetaxel chemotherapy. Recently, results of a phase III trial comparing abiraterone plus prednisone vs placebo plus prednisone in asymptomatic and without visceral metastasis, castration-resistant metastatic prostate cancer patients, demonstrated a better radiological progression free survival for abiraterone treated patients and a trend towards a better survival was clear for abiraterone treated patients.

No clinical evidence exists about efficacy of chemotherapy and antiandrogen therapy combination. All trials have been performed in patients in which LHRH agonist treatment was continued although there is not clear evidence about efficacy of hormonal treatment. Some retrospective studies suggest that androgen deprivation treatment should be maintained in chemotherapy treated patients. Abiraterone has been proved to suppress androgen levels to negative values, and to add efficacy to castration hormonal therapy. Combination of abiraterone with docetaxel chemotherapy seems promising adding efficacy to only docetaxel chemotherapy. A randomized phase II study comparing docetaxel + prednisone + abiraterone to docetaxel + prednisone in mCRPC in patients treated previously with abiraterone, seems promising to explore addition of efficacy to taxotere after abiraterone hormonal treatment.

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d; Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Córdoba, Spain, 14004
    • Complejo Hospitalario Regional Reina Sofía
  • Guadalajara, Spain, 19002
    • Hospital Universitario de Guadalajara
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Málaga, Spain, 29010
    • Hospital Virgen de la Victoria
  • Sevilla, Spain, 41013
    • Complejo Hospitalario regional Virgen del Rocio
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Castellón
    • Castellón de la Plana, Castellón, Spain, 12002
      • Consorcio Hospitalario Provincial de Castellón
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07120
      • Hospital Universitari Son Espases
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36036
      • Complexo Hospitalario Universitario de Vigo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Male aged 18 years and above
• Histologically or cytologically confirmed adenocarcinoma of the prostate.
• Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI.
• Prostate cancer progression to previous castration treatment documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria or bone scan progression
• Asymptomatic or mildly symptomatic from prostate cancer
• Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM).
• Previous anti-androgen therapy and progression after withdrawal.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Hemoglobin >= 10.0 g/dL independent of transfusion
• Platelet count >= 100,000/µL
• Serum albumin >= 3.5 g/dL
• Serum creatinine < 1.5 x ULN or a calculated creatinine clearance >= 60 mL/min
• Serum potassium >= 3.5 mmol/L
• Liver function: a. Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease) b. AST or ALT < 2.5 x ULN
• Life expectancy of at least 6 months
• Patients who have partners of childbearing potential must be willing to use a method of birth control

Exclusion Criteria:

• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily.
• Pathological finding consistent with small cell carcinoma of the prostate
• Liver or visceral organ metastasis
• Known brain metastasis
• Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1
• Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
• Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day
• Radiation or radionuclide therapy for treatment of metastatic CRPC
• Previously treated with ketoconazole for prostate cancer for greater than 7 days
• Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
• Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1
• Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1
• Uncontrolled hypertension (systolic BP >= 160 mmHg or diastolic BP >= 95 mmHg).
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Clinically significant heart disease
• Atrial Fibrillation, or other cardiac arrhythmia requiring therapy
• Other malignancy, except non-melanoma skin cancer, with a >= 30% probability of recurrence within 24 months
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
• Any condition which, in the opinion of the investigator, would preclude participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d	Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d; Docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d in 21 day cycles.; Other Names: Arm A
Active Comparator: Arm B; docetaxel 75 mg/m2 + prednisone 10 mg/d	Drug: docetaxel 75 mg/m2 + prednisone 10 mg/d; Docetaxel 75 mg/m2 plus prednisone 10 mg/d in 21 day cycles.; Other Names: Arm B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year radiologic progression free survival	Time from randomization to radiologic disease progression	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death	Up to 3 years
Radiologic progression free survival	Time from randomization to radiologic progression free survival	Up to 1 year
PSA progression free survival	Time from randomization to PSA progression	Up to 3 weeks
PSA response rate	50% & 90% PSA reduction from randomisation	Up to 3 weeks
Objective response rate	Response according RECIST criteria	Up to 12 weeks
Quality of life rate	Quality of life according to FACT-P questionaire	Up to 12 weeks
Time to skeletal-related event	Time from randomization to skeletal-related events	Up to 12 weeks
Time to opiate use for cancer pain	Time from randomization to opiate use for cancer pain	Up to 3 weeks
Time to pain progression	Time from randomization to pain progression defined as an increase in median BPI score ≥ 30% from baseline	Up to 3 weeks
Safety profile	Related adverse events per patient	Up to 3 weeks

Collaborators and Investigators

• Sponsor: Spanish Oncology Genito-Urinary Group
• Collaborators: Apices Soluciones S.L.; Janssen, LP
• Investigators: Study Chair: Miguel A Climent, MD, Fundación Instituto Valenciano de Oncología; Principal Investigator: José A Arranz, MD, HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN, Servicio de Oncología Médica; Principal Investigator: Daniel E Castellano, MD, HOSPITAL UNIVERSITARIO 12 DE OCTUBRE,Servicio de Oncología Médica; Principal Investigator: Begoña Mellado, MD, HOSPITAL CLINIC I PROVINCIAL DE BARCELONA, Servicio de Oncología Médica; Principal Investigator: Albert Font, MD, HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL, Servicio de Oncología Médica; Principal Investigator: Alfredo Sánchez, MD, CONSORCIO HOSPITALARIO PROVINCIAL DE CASTELLÓN, Servicio de Oncología Médica; Principal Investigator: Emilio Esteban, MD, HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS, Servicio de Oncología Médica; Principal Investigator: María I Sáez, MD, HOSPITAL VIRGEN DE LA VICTORIA, Servicio de Oncología Médica; Principal Investigator: Carmen Santander, MD, HOSPITAL UNIVERSITARIO MIGUEL SERVET, Servicio de Oncología Médica; Principal Investigator: Pablo Maroto, MD, HOSPITAL DE LA SANTA CREU I SANT PAU, Servicio de Oncología Médica; Principal Investigator: Carmen Garcias de España, MD, HOSPITAL UNIVERSITARI SON ESPASES, Servicio de Oncología Médica; Principal Investigator: Teresa Alonso, MD, HOSPITAL RAMÓN Y CAJAL, Servicio de Oncología Médica; Principal Investigator: Javier Puente, MD, Hospital Clínico San Carlos, Servicio de Oncología Médica; Principal Investigator: Martín Lázaro, Md, COMPLEXO HOSPITALARIO UNIVERSITARIO DE VIGO, Servicio de Oncología Médica; Principal Investigator: Javier Cassinello, MD, HOSPITAL UNIVERSITARIO DE GUADALAJARA, Servicio de Oncología Médica; Principal Investigator: María J Méndez, MD, COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA, Servicio de Oncología Médica; Principal Investigator: Begoña Perez-Valderrama, MD, COMPLEJO HOSPITALARIO REGIONAL VIRGEN DEL ROCIO, Servicio de Oncología Médica

Publications and helpful links

General Publications

• Climent MA, Font A, Duran I, Puente J, Jose Mendez-Vidal M, Saez MI, Santander Lobera C, Angel Arranz Arija J, Gonzalez-Del-Alba A, Sanchez-Hernandez A, Juan Fita MJ, Esteban E, Alonso-Gordoa T, Mellado Gonzalez B, Maroto P, Lazaro-Quintela M, Cassinello-Espinosa J, Perez-Valderrama B, Garcias C, Castellano D. A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. Eur J Cancer. 2022 Nov;175:110-119. doi: 10.1016/j.ejca.2022.08.002. Epub 2022 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2014
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Metastatic prostate cancer; Abiraterone acetate
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Disease Progression; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: ABIDO-SOGUG; 2013-003811-23 (EudraCT Number)